CoCrMo nanoparticle induces neurotoxicity mediated via mitochondrial dysfunction: a study model for implant derived...

Area of Science:

• Biomaterials Science
• Neuroscience
• Cell Biology

Background:

• Elevated cobalt-chromium-molybdenum (CoCrMo) nanoparticles from total hip replacements (THR) are linked to patient toxicity.
• Recent studies indicate these nanoparticles may induce polyneuropathy in THR patients.

Purpose of the Study:

• To investigate the molecular mechanisms of CoCrMo nanoparticle-induced mitochondrial dysfunction in neurons.
• To utilize induced pluripotent stem cell-derived neurons (iPSC neurons) for detailed analysis.

Main Methods:

• CoCrMo nanoparticle treatment of telencephalic iPSC-derived neurons.
• Assessment of mitochondrial membrane potential and superoxide generation.
• Gene expression analysis of oxidative stress markers.
• Mitochondrial morphology and dynamics tracking via live cell imaging.
• Protein analysis of mitochondrial fission/fusion markers (Drp-1, Mfn-2).

Main Results:

• CoCrMo nanoparticles caused a dose-dependent decrease in mitochondrial membrane potential and superoxide generation.
• Significant upregulation of oxidative stress-related genes was observed.
• Mitochondrial area, perimeter, and length were reduced, with decreased movement.
• Increased mitochondrial fission (upregulated Drp-1, downregulated Mfn-2) was confirmed at the protein level.

Conclusions:

• CoCrMo nanoparticles significantly disrupt neuronal mitochondrial dynamics.
• This disruption impairs energy production, elevates oxidative stress, and restricts mitochondrial movement.
• These effects suggest a potential pathway for CoCrMo-induced neurodegeneration.